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arXiv 2004.04935q-bio.TOq-bio.GN
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冠状病毒受体及相关因子在人胚胎发育中的单细胞RNA表达图谱

A single-cell RNA expression map of coronavirus receptors and associated factors in developing human embryos

Stacy Colaco, Karisma Chhabria, Domdatt Singh, Anshul Bhide, Neha Singh, Abhishek Singh, Atahar Husein, Anuradha Mishra, Richa Sharma, Nancy Ashary, Deepak Modi

摘要:

为了预测发育中的人类胚胎是否允许冠状病毒,我们分析了针对冠状病毒受体(ACE 2、BSG、DPP 4和ANPEP)、刺突蛋白切割酶(TMPRSS 2、CTSL)的受精卵、4细胞、8细胞、桑椹胚、内细胞团、上胚层、原始内胚层和滋养外胚层的公开可用的单细胞RNA-seq数据集。我们还分析了参与病毒复制的宿主基因的存在,运输所需的内体分选复合物(ESCRT)和SARS-Cov-2相互作用。结果表明,ACE 2、BSG、DPP 4和ANPEP在受精卵至囊胚包括滋养外胚层谱系的细胞中表达。ACE 2、TMPRSS、BSG和CTSL在一定比例的上胚层细胞和大多数滋养外胚层细胞中共转录。胚胎和滋养外胚层细胞还表达蛋白质ESCRT、病毒复制以及与SARS-CoV-2相互作用的基因。我们鉴定了在ACE 2和TMPRSS 2共表达细胞中富集的上胚层中的1985个基因和滋养外胚层中的1452个基因;其中216个基因在两种细胞类型中是共同的。这些基因与脂质代谢、溶酶体、过氧化物酶体和氧化磷酸化途径有关。总之,我们的研究结果表明,发育中的人类胚胎可能允许冠状病毒通过经典和非经典机制进入,并且它们还表达参与病毒内吞和复制的蛋白质的基因。这些知识将有助于在COVID-19大流行期间对IVF患者进行循证管理。

英文摘要:

To predict if developing human embryos are permissive to coronaviruses, we analyzed publicly available single cell RNA-seq datasets of zygotes, 4-cell, 8-cell, morula, inner cell mass, epiblast, primitive endoderm and trophectoderm for the coronavirus receptors (ACE2, BSG, DPP4 and ANPEP), the Spike protein cleavage enzymes (TMPRSS2, CTSL). We also analyzed the presence of host genes involved in viral replication, the endosomal sorting complexes required for transport (ESCRT) and SARS-Cov-2 interactions. The results reveal that ACE2, BSG, DPP4 and ANPEP are expressed in the cells of the zygote, to blastocyst including the trophectodermal lineage. ACE2, TMPRSS, BSG and CTSL are co-transcribed in a proportion of epiblast cells and most cells of the trophectoderm. The embryonic and trophectodermal cells also express genes for proteins ESCRT, viral replication and those that interact with SARS-CoV-2. We identified 1985 genes in epiblast and 1452 genes in the trophectoderm that are enriched in the ACE2 and TMPRSS2 co-expressing cells; 216 genes of these are common in both the cell types. These genes are associated with lipid metabolism, lysosome, peroxisome and oxidative phosphorylation pathways. Together our results suggest that developing human embryos could be permissive to coronavirus entry by both canonical and non-canonical mechanisms and they also express the genes for proteins involved in viral endocytosis and replication. This knowledge will be useful for evidence-based patient management for IVF during the COVID-19 pandemic.

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